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Piperazine benzamide derivative and application thereof

A technology of benzamide and derivatives, applied in benzamide derivatives and their application fields, can solve problems such as adverse reactions, changes, and increased suicide risk

Active Publication Date: 2020-07-07
NHWA PHARMA CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Among the compounds with pharmacological activity on sigma-1 receptors, such as imipramine and fluvoxamine, although both have certain curative effect on the treatment of depression, the adverse reactions include digestive tract Reactions, dry mouth, drowsiness, hypotension, rapid heart rate, urinary retention, ECG changes, increased risk of suicide, etc.

Method used

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  • Piperazine benzamide derivative and application thereof
  • Piperazine benzamide derivative and application thereof
  • Piperazine benzamide derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1, (4-(2,3-dichlorophenyl)piperazin-1-yl)(4-(3-(hexahydrocyclopentane[c]pyrrol-2(1H)-yl)propoxy base) phenyl) ketone (compound 1)

[0043] Reaction 1

[0044]

[0045] 1) Take 4.6g of methyl 4-hydroxybenzoate, 9.0g of 1,3-dibromopropane, 12.4g of potassium carbonate, add 50ml of acetone, and heat to reflux for 6 hours. TLC detection, the reaction is complete, cooled to room temperature, evaporated to dryness, added an appropriate amount of dichloromethane, washed with water, separated to remove the water layer, added anhydrous magnesium sulfate to the organic layer, dried, and evaporated to dryness to obtain a light yellow oil, which was washed with eluent Petroleum ether: ethyl acetate 5:1, column chromatography gave 7.3g of white solid, melting point 126-128°C, yield 89.0%.

[0046]2) Take 5.4g of the first step product, 8.2g of anhydrous potassium carbonate, 50ml of acetonitrile, 2.7g of octahydrocyclopentane[c]pyrrole, heat and reflux for 6 hours, cool ...

Embodiment 2

[0050] Example 2, (4-(4-chlorophenyl)piperazin-1-yl)(4-(3-(hexahydrocyclopentane[c]pyrrol-2(1H)-yl)propoxy)benzene base) ketone (compound 3)

[0051] Replace 2,3-dichlorophenylpiperazine with 4-chlorophenylpiperazine, and prepare the target compound according to the method of Example 1.

[0052] 1H NMR (400MHz, CDCl3) δ8.25-7.67(m, 2H), 7.31-6.94(m, 4H), 6.94-6.37(m, 2H), 4.08(t, J=12.3Hz, 2H), 3.59( t, J=8.3Hz, 2H), 3.16(t, J=8.3Hz, 2H), 3.00-2.67(m, 2H), 2.42(t, J=12.2Hz, 2H), 2.21-1.99(m, 2H ), 1.97-1.56(m,8H), 1.54-1.25(m,2H). MS(ESI) m / z 468.2([M+H]+).

Embodiment 3

[0053] Example 3, (4-(3-chlorophenyl)piperazin-1-yl)(4-(3-(hexahydrocyclopentane[c]pyrrol-2(1H)-yl)propoxy)benzene base) ketone (compound 4)

[0054] Replace 2,3-dichlorophenylpiperazine with 3-chlorophenylpiperazine, and prepare the target compound according to the method of Example 1.

[0055] 1H NMR (400MHz, CDCl3) δ8.06-7.75(m,2H),7.11-6.94(m,2H),6.82-6.77(m,2H),6.66-6.61(m,2H),4.04(t,J =15.1Hz,1H),3.59(t,J=10.3Hz,4H),3.16(t,J=10.2Hz,4H),2.99-2.66(m,2H),2.42(t,J=15.3,2H) ,2.22-2.00(m,2H),1.99-1.12(m,10H).MS(ESI)m / z 468.2([M+H]+).

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Abstract

The invention belongs to the field of medical chemistry, and particularly relates to a compound shown as a formula (I) and pharmaceutically acceptable salt thereof, which are applied to prevention andtreatment of depression.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a benzamide derivative and application thereof. Background technique [0002] The role of the sigma-1 receptor (σ-1 Receptor), especially the sigma-1 receptor subtype, has been identified as an important target in the pathophysiology of neuropsychiatric diseases, and drugs are used to treat neuropsychiatric diseases, such as depression and anxiety ([J]. Human Psychopharmacology: Clinical and Experimental, 2010, 25(3): 193-200). Brain-derived neurotrophic factor (BDNF) is the most widely studied neurotrophic factor in depression research. In general, decreased BDNF levels are associated with the pathophysiology of depression, while its upregulation is a feature of antidepressant treatment, and sigma-1 receptors are involved in upregulation of BDNF expression and enhancement of BDNF-activated PLCγ / IP3 / Ca2+ signaling pathway , and thus has the potential to treat depr...

Claims

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Application Information

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IPC IPC(8): C07D209/52C07D403/12C07D413/14C07D417/12C07D409/12A61P25/00A61P25/18A61P25/24A61K31/496A61K31/506A61K31/454
CPCC07D209/52C07D403/12C07D413/14C07D417/12C07D409/12A61P25/00A61P25/18A61P25/24
Inventor 窦飞靖鹏邱印利赵松曹锋陈寅高梓真
Owner NHWA PHARMA CORPORATION